# Transcription factors in kidney development

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $663,643

## Abstract

The goal of this study is to investigate the regulatory networks controlled by Eya1 and its cofactors, as
well as their occupancy of cis-regulatory DNA elements (CREs), in nephron formation. Eya1 is a
transcriptional coactivator with intrinsic phosphatase activity that regulates gene expression through
interactions with DNA-binding proteins, since it does not bind DNA directly. Our previous work has
shown that Eya1 forms critical transcriptional complexes with Six1/4, Six2, Myc, and the SWI/SNF
chromatin remodeling complex to specify the metanephric mesenchyme and maintain nephron
progenitors. Recently, we identified Eya1-regulated genes, associated proteins, and occupied CREs,
including interactions with chromatin regulators other than the SWI/SNF family, cell cycle regulators,
and DNA replication and repair proteins. Notably, we found that Eya1 interacts with multiple
components of the transcriptional repressor REST (RE1 silencing transcription factor) complex and
identified the REST-binding RE1 site in 76% of Eya1-occupied CREs without H3K27ac-deposition.
This RE1 site was present in ~45% of Eya1 target genes that were upregulated in Eya1-deficient
nephron progenitors, suggesting that Eya1 may act as a corepressor associated with Rest-dependent
gene repression networks. Moreover, more than half of the identified Wilms tumor-associated genes
are binding partners or targeted genes of Eya1. This renewal application proposes further studies to
investigate the importance of Eya1-occupied CREs containing Rest-binding RE1 sites in maintaining
nephron progenitor cell identity and how Eya1-BAF interaction regulates nephron progenitor cell
identity/state and commitment. This research represents a crucial step in understanding how Eya1
activity is amplified and diversified by its cofactors and CRE occupancy to activate or silence gene
expression that is crucial for establishing and maintaining nephron progenitor cells. The results will
provide new insights into how dysfunction of the Eya1-regulatory network contributes to kidney
diseases, including Wilms tumor.

## Key facts

- **NIH application ID:** 10812799
- **Project number:** 2R01DK064640-19A1
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** PIN-XIAN XU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $663,643
- **Award type:** 2
- **Project period:** 2003-08-15 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10812799

## Citation

> US National Institutes of Health, RePORTER application 10812799, Transcription factors in kidney development (2R01DK064640-19A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10812799. Licensed CC0.

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